ArticleNature communications2023
Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Unpacking boxes: identification of novel inhibitors of malaria parasite invasion.International journal for parasitology. Drugs and drug resistance · 2026Article
- Minimum Inoculum of Resistance Assay for Evaluating Antitoxoplasmosis Compounds That Target Phenylalanine tRNA Synthetase.ACS infectious diseases · 2026Article
- Efficacy, Structure-Activity Relationship, and Mode of Action Studies of a New Generation of Acridine/Acridone-Based Antimalarials.ACS infectious diseases · 2026Article
- Potent reaction hijacking inhibitors ofbioRxiv : the preprint server for biology · 2026Article
- Identification of an Orally Efficacious Imidazo[4,5-Journal of medicinal chemistry · 2026Article
- Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.Nature communications · 2026Article
- Minimum inoculum of resistance assay for evaluating for anti-toxoplasmosis compounds that target phenyl alanine tRNA synthetase.bioRxiv : the preprint server for biology · 2026Article
- High throughput quantitative tracking ofbioRxiv : the preprint server for biology · 2026Article
- Article
- Plasmodium falciparum DNA repair dynamics reveal unique roles for TLS polymerases and PfRad51 in genome diversification.Nucleic acids research · 2025Article
- PfATP2 is a flippase on the Plasmodium falciparum surface that is important for growth and influences parasite sensitivity to antiplasmodial compounds.PLoS pathogens · 2025Article
- Characterizing the quick-killing mechanism of action of azithromycin analogs against malaria parasites.Antimicrobial agents and chemotherapy · 2025Article
- Article
- Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4.Journal of medicinal chemistry · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- Fungal-derived methyldeoxaphomins targetProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Quinoxaline-based anti-schistosomal compounds have potent anti-plasmodial activity.PLoS pathogens · 2025Article
- YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates.Scientific reports · 2025Article
- TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent AntimalarialJournal of medicinal chemistry · 2025Article
- Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4.ChemMedChem · 2024Article
Corrections and comments
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Authors and funding
25 authors at 10 institutions in 7 countries.
Funding
Abstract
In vitro evolution of drug resistance is a powerful approach for identifying antimalarial targets, however, key obstacles to eliciting resistance are the parasite inoculum size and mutation rate. Here we sought to increase parasite genetic diversity to potentiate resistance selections by editing catalytic residues of Plasmodium falciparum DNA polymerase δ. Mutation accumulation assays reveal a ~5-8 fold elevation in the mutation rate, with an increase of 13-28 fold in drug-pressured lines. Upon challenge with the spiroindolone PfATP4-inhibitor KAE609, high-level resistance is obtained more rapidly and at lower inocula than wild-type parasites. Selections also yield mutants with resistance to an "irresistible" compound, MMV665794 that failed to yield resistance with other strains. We validate mutations in a previously uncharacterised gene, PF3D7_1359900, which we term quinoxaline resistance protein (QRP1), as causal for resistance to MMV665794 and a panel of quinoxaline analogues. The increased genetic repertoire available to this "mutator" parasite can be leveraged to drive P. falciparum resistome discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.